American Journal of Nephrology最新文献

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Association between Serum Zinc Levels and Trabecular Bone Scores among Patients Undergoing Chronic Hemodialysis. 慢性血液透析患者血清锌水平与骨小梁评分的关系。
IF 3.2 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2025-01-24 DOI: 10.1159/000543756
Mayuko Hori, Hiroshi Takahashi, Chika Kondo, Asami Takeda, Kunio Morozumi, Shoichi Maruyama, Mayuko Hori
{"title":"Association between Serum Zinc Levels and Trabecular Bone Scores among Patients Undergoing Chronic Hemodialysis.","authors":"Mayuko Hori, Hiroshi Takahashi, Chika Kondo, Asami Takeda, Kunio Morozumi, Shoichi Maruyama, Mayuko Hori","doi":"10.1159/000543756","DOIUrl":"10.1159/000543756","url":null,"abstract":"<p><strong>Introduction: </strong>Zinc, an essential trace element, plays an important role in various cellular processes, and zinc deficiency is common in patients undergoing hemodialysis. Zinc has been shown to stimulate osteoblastic bone formation and mineralization and inhibit osteoclastic bone resorption. Although osteoporosis is highly prevalent among patients undergoing hemodialysis, the utility of areal bone mineral density (aBMD) measured using dual-energy X-ray absorptiometry (DXA) is limited because DXA cannot reveal bone microarchitectural alterations. The trabecular bone score (TBS) extracted from DXA images is a new texture measurement used to assess the bone microarchitecture. However, whether zinc status is associated with TBS in patients undergoing hemodialysis remains unclear. Therefore, we investigated the association between serum zinc levels and osteoporosis parameters (aBMD and TBS) in patients undergoing chronic hemodialysis.</p><p><strong>Methods: </strong>This cross-sectional study included 316 outpatients undergoing hemodialysis at the Masuko Memorial Hospital in Japan. Serum zinc levels were measured, and aBMD and TBS were assessed using DXA.</p><p><strong>Results: </strong>In total, 139 (41.0%) patients had zinc deficiency, defined as serum zinc levels <60 µg/dL. In multivariate linear regression analyses, high serum zinc levels were associated with high TBS (β = 0.146, p = 0.004) but not aBMD values (total hip aBMD: β = -0.0200, p = 0.63; lumbar spine aBMD: β = 0.0478, p = 0.34). In multiple logistic regression analysis, zinc deficiency was associated with degraded bone microarchitecture according to the TBS (odds ratio, 2.27; 95% confidence interval, 1.22-4.22; p = 0.009). No association was found between the serum zinc status and aBMD thresholds for osteoporosis.</p><p><strong>Conclusion: </strong>These results suggest that zinc plays a protective role in bone metabolism by inhibiting chronic kidney disease-induced changes in the bone microarchitecture.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"468-474"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Trends and the Role of Gene-Environment Interactions in Idiopathic Membranous Nephropathy in Northern China. 中国北方特发性膜性肾病基因-环境相互作用的趋势和作用。
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2024-12-03 DOI: 10.1159/000542910
Wanyin Hou, Sufang Shi, Zhe Yan, Maodong Liu, Gengxin Guo, Yujing Zhang, Yun Dong, Junjie Gao, Fuyun Sun, Guicai Hu, Zhaoxia Zheng, Liping Duan, Haisong Zhang, Bing Liu, Shaomei Li, Sumin Jiao, Jinwei Wang, Zhao Cui, Suxia Wang, Ying Li, Shuxia Fu, Minghui Zhao
{"title":"Trends and the Role of Gene-Environment Interactions in Idiopathic Membranous Nephropathy in Northern China.","authors":"Wanyin Hou, Sufang Shi, Zhe Yan, Maodong Liu, Gengxin Guo, Yujing Zhang, Yun Dong, Junjie Gao, Fuyun Sun, Guicai Hu, Zhaoxia Zheng, Liping Duan, Haisong Zhang, Bing Liu, Shaomei Li, Sumin Jiao, Jinwei Wang, Zhao Cui, Suxia Wang, Ying Li, Shuxia Fu, Minghui Zhao","doi":"10.1159/000542910","DOIUrl":"10.1159/000542910","url":null,"abstract":"<p><strong>Introduction: </strong>Idiopathic membranous nephropathy (iMN) has become one of the most prevalent primary glomerular diseases, with a marked increase in prevalence over the past two decades in northern China. Fine particulate matter (PM2.5) is considered to be associated with this rising prevalence. In this study, we aimed to evaluate the trends of iMN in relation to improved air quality and conduct a cross-sectional study in Hebei province (northern China, near Beijing) to investigate the role of gene-environment interactions in its development.</p><p><strong>Methods: </strong>This study established two cohorts. Cohort 1 included 22,937 pathology reports from Peking University First Hospital (2002-2021) to assess iMN prevalence. Cohort 2 comprised 5,635 iMN patients from 11 cities in Hebei province (2009-2013). DNA samples from 374 iMN patients and 1,259 controls were genotyped for SNPs rs4664608 (PLA2R1) and rs2187668 (HLA-DQA1). Patients were stratified by air pollution risk levels. The annual percentage change (APC) and average annual percentage change were estimated using a joinpoint regression model. Gene-environment interactions were analyzed using logistic regression and epinet calculation.</p><p><strong>Results: </strong>In cohort 1, 5,586 patients with iMN were identified, representing 24.3% of the 22,937 patients from 2002 to 2021. The general population showed a significant increase in iMN proportion with an APC of +12.7% per year from 2002 to 2014 (95% CI: 10.3-17.5, p < 0.001), followed by a decline with an APC of -5.6% per year from 2014 to 2021 (95% CI: -9.6 to -2.6, p < 0.001). In Hebei province, the iMN frequency rose significantly with an APC of +17.6% per year from 2002 to 2016 (95% CI: 14.5-28.6, p < 0.001), peaking at 60%, and then declined with an APC of -5.5% per year from 2016 to 2021 (95% CI: -13.1 to -1.2, p = 0.02). Cohort 2 highlighted significant regional variation in iMN incidence across Hebei province. Geographic exposure to pollution was identified as an independent risk factor for iMN (RR: 1.49, 95% CI: 1.38-1.56, p < 0.001). Gene-environment interaction analysis revealed that patients with risk alleles in the PLA2R1 gene and exposure to risk environments had a markedly increased risk of developing iMN (odds ratio = 38.72, 95% CI: 11.95-125.46, p < 0.01).</p><p><strong>Conclusion: </strong>The annual growth rate of iMN in northern China appears to be slowing down. Gene-environment interactions may have contributed to the previously observed increase in prevalence.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"148-157"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Incidence of Adult Primary Immunoglobulin A Nephropathy among a Racially/Ethnically Diverse Population in the United States. 美国种族/族裔多元化人群中成人原发性免疫球蛋白 A 肾病的发病率。
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2024-11-04 DOI: 10.1159/000541869
John J Sim, Qiaoling Chen, Nancy Cannizzaro, Simran K Bhandari, Ancilla W Fernandes, John Chang, Cibele Pinto, Asher D Schachter, Mohit Mathur
{"title":"Incidence of Adult Primary Immunoglobulin A Nephropathy among a Racially/Ethnically Diverse Population in the United States.","authors":"John J Sim, Qiaoling Chen, Nancy Cannizzaro, Simran K Bhandari, Ancilla W Fernandes, John Chang, Cibele Pinto, Asher D Schachter, Mohit Mathur","doi":"10.1159/000541869","DOIUrl":"10.1159/000541869","url":null,"abstract":"<p><strong>Introduction: </strong>IgA nephropathy (IgAN), a leading cause of kidney failure worldwide, is one of the most common forms of primary glomerulonephropathy with variability by race and ethnicity. Using a diverse cohort within a large integrated health system in the United States (US), we identified and characterized patients with biopsy-proven IgAN and report annual incidence rates across racial/ethnic groups and standardized to the US nationally.</p><p><strong>Methods: </strong>A cross-sectional study between January 1, 2010, and December 31, 2021 within Kaiser Permanente Southern California was performed. Patients (age >/=18 years) who underwent a native kidney biopsy and identified as having primary IgAN comprised the study population. Laboratory, demographic, and comorbidity information were obtained from the electronic health records. Annual incidence rates were calculated for biopsy-proven IgAN (per 100,000 person-years) and standardized to 2020 US Census.</p><p><strong>Results: </strong>Of 9,392 individuals who underwent kidney biopsy, 606 adult patients were identified with primary IgAN. Crude annual IgAN incidence rates ranged from 1.3 to 2.2 (per 100,000 person-years). US census standardized incidence rate (CI) of IgAN was 1.4 (0.8, 2.0) per 100,000 person-years in the 12-year period. Incidence rate (per 100,000 person-years) was highest among Asian/Pacific Islander (4.5) and Hispanic (1.7) patients and lowest among White (1.2) and Black (0.6) patients. Median estimated glomerular filtration rate (eGFR) was 51 mL/min with median urine protein creatinine ratio (uPCR) 1.8 g/g.</p><p><strong>Conclusion: </strong>Among a large diverse US population within Southern California, we observed an IgAN incidence rate of 1.7 which estimated to a standardized US incidence of 1.4 (per 100,000 person-years) within a 12-year period. Patients appear to be diagnosed at more advanced disease given kidney function and proteinuria at biopsy.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"172-177"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exosomal Specificity of MiR-15a-5p as Marker of Activity, Renal Damage, and Disease Flares in Systemic Lupus Erythematosus. MiR-15a-5p作为系统性红斑狼疮活性、肾损害和疾病发作标志物的外泌体特异性
IF 3.2 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2025-03-13 DOI: 10.1159/000544854
Ana Ortega, Ana Flores-Chova, Olga Martinez-Arroyo, Ana Puertes, Sara Vela-Bernal, Jose Luis Gorriz, Miguel A Solis-Salguero, Liria Terradez, Ana Ortega, Maria J Forner, Raquel Cortes
{"title":"Exosomal Specificity of MiR-15a-5p as Marker of Activity, Renal Damage, and Disease Flares in Systemic Lupus Erythematosus.","authors":"Ana Ortega, Ana Flores-Chova, Olga Martinez-Arroyo, Ana Puertes, Sara Vela-Bernal, Jose Luis Gorriz, Miguel A Solis-Salguero, Liria Terradez, Ana Ortega, Maria J Forner, Raquel Cortes","doi":"10.1159/000544854","DOIUrl":"10.1159/000544854","url":null,"abstract":"<p><strong>Introduction: </strong>Little is known about the biofluid specificity of microRNAs (miRNAs) in systemic lupus erythematosus (SLE) and the biofluid influence on miRNA diagnosis and prognosis accuracy. Our aim was to analyze the effect of biofluid on miRNA expression and to identify a specific miRNA profile in plasma exosomes related to SLE activity, renal damage, and disease flares over a 60-month follow-up period.</p><p><strong>Methods: </strong>Noncoding RNA-sequencing analysis was used to determine miRNA in plasma and plasma exosomes in a discovery cohort of SLE patients and controls. Potential miRNAs were selected based on the differential expression between biofluids and were validated by quantitative polymerase chain reaction in a higher validation cohort.</p><p><strong>Results: </strong>From the small RNA sequencing, the 25 miRNAs with the highest fold-change expression between biofluids were identified. Nine miRNAs were validated in a larger cohort (n = 115, of whom 30 had nephritis) and were found to be increased in exosomal fraction and patient groups. Further analysis revealed a panel combining three miRNAs for lupus nephritis diagnosis (miR-101-3p, miR-144-5p, and miR-15a-5p) gave an area under the curve that improves the readout of the single miRNAs (0.964, p < 0.0001). However, only miR-15a-5p had a strong discriminatory power of renal injury between patients (0.81, p < 0.0001). Finally, exosomal miR-15a-5p was associated with histological features, chronicity index and flares (odds ratio 4.24, p < 0.001), high levels being a strong independent predictor of 60-month follow-up flares (hazard ratio 4.24, p < 0.001).</p><p><strong>Conclusion: </strong>This novelty study demonstrated a biofluid exosome specificity of miRNA profile related to SLE with nephritis, highlighting exosomal miR-15a-5p levels with a strong association with proteinuria, renal histological features, and high accuracy in the diagnosis of renal damage and detection of lupus flares. The detection of altered miRNAs levels in exosome-enriched fraction improved the diagnostic accuracy of renal damage in SLE.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"529-542"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Relationship between Cumulative Exposure and Time Course of Plasma Aldosterone Concentrations and Chronic Kidney Disease in Hypertensive Patients: A Real-World Cohort Study. 高血压患者血浆醛固酮浓度累积暴露和时间过程与慢性肾脏疾病的关系:一项真实世界队列研究
IF 3.2 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2025-03-29 DOI: 10.1159/000545451
Nanfang Li, Shuaiwei Song, Xintian Cai, Di Shen, Junli Hu, Qing Zhu, Huimin Ma, Yingying Zhang, Rui Ma, Pan Zhou, Zhiqiang Zhang, Wenbo Yang, Wen Jiang, Jing Hong, Delian Zhang, Nanfang Li
{"title":"Relationship between Cumulative Exposure and Time Course of Plasma Aldosterone Concentrations and Chronic Kidney Disease in Hypertensive Patients: A Real-World Cohort Study.","authors":"Nanfang Li, Shuaiwei Song, Xintian Cai, Di Shen, Junli Hu, Qing Zhu, Huimin Ma, Yingying Zhang, Rui Ma, Pan Zhou, Zhiqiang Zhang, Wenbo Yang, Wen Jiang, Jing Hong, Delian Zhang, Nanfang Li","doi":"10.1159/000545451","DOIUrl":"10.1159/000545451","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to investigate the effects of cumulative exposure to plasma aldosterone concentration (PAC) and its time course on chronic kidney disease (CKD) in hypertensive patients, with the goal of providing insights into preventing future CKD events, especially in younger hypertensive patients.</p><p><strong>Methods: </strong>This study enrolled a total of 7,142 hypertensive participants, each of whom had undergone at least two PAC measurements before the age of 60. We calculated the annual PAC area under the curve (AUC) and used Cox regression analyses to examine the association between annual PAC_AUC and CKD risk. We also explored how the timing course of PAC accumulation affected CKD risk, as different stages of PAC accumulation, even with the same annual PAC_AUC, may lead to varying risks. Additionally, we conducted a comparative analysis to assess the predictive performance of annual PAC_AUC versus single PAC measurements.</p><p><strong>Results: </strong>During a median follow-up of 5.83 years, 754 participants developed CKD. The results showed a progressive increase in CKD risk with higher annual PAC_AUC (hazard ratio: 1.19; 95% confidence interval: 1.17, 1.21). Moreover, the timing course of PAC accumulation modulates this risk; Kaplan-Meier curves indicated that participants with similar annual PAC_AUC, but earlier PAC exposure had a higher CKD risk compared to those exposed later (Log-rank test, p < 0.001). Furthermore, annual PAC_AUC outperformed single PAC measurements in predictive accuracy.</p><p><strong>Conclusion: </strong>CKD risk is influenced by both annual PAC_AUC and the time course of PAC exposure. Participants exposed to elevated PAC earlier had a higher CKD risk than those exposed later, even at the same annual PAC_AUC. This highlights the importance of early PAC control to prevent CKD.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"641-656"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adverse Prognosis in Membranous Nephropathy with Phospholipase A2 Receptor 1 Epitope Spreading: A Prospective Study. PLA2R1表位扩散的膜性肾病不良预后:一项前瞻性研究。
IF 3.2 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2025-03-17 DOI: 10.1159/000545133
Qijun Wan, Liling Wu, Zhihang Su, Bo Tang, Yuna Chen, Haofei Hu, Yuan Cheng, Jianyu Chen, Qijun Wan
{"title":"Adverse Prognosis in Membranous Nephropathy with Phospholipase A2 Receptor 1 Epitope Spreading: A Prospective Study.","authors":"Qijun Wan, Liling Wu, Zhihang Su, Bo Tang, Yuna Chen, Haofei Hu, Yuan Cheng, Jianyu Chen, Qijun Wan","doi":"10.1159/000545133","DOIUrl":"10.1159/000545133","url":null,"abstract":"<p><strong>Introduction: </strong>In primary membranous nephropathy (MN), 80% of patients harbor antibodies (Abs) against phospholipase A2 receptor 1 (PLA2R1), closely linked to disease prognosis. Prior research has validated the correlation between Abs directed toward the cysteine-rich (CysR) and C-type lectin 1, 7, and 8 (CTLD1, CTLD7, and CTLD8) domains of PLA2R1 and outcomes in MN.</p><p><strong>Methods: </strong>In a prospective cohort of 52 patients with newly diagnosed PLA2R1-MN, with urine protein ≥ 3.5 g/24 h and estimated glomerular filtration rate ≥30 mL/min/1.73 m2, we studied epitope spreading patterns and domain-specific PLA2R1-Ab clinically using Western blot and ELISA. The primary outcome was a combination of remission at 12 months. Kaplan-Meier curves and multivariable Cox regression were employed to compare the single and multiple epitope patients.</p><p><strong>Results: </strong>All patients had anti-CysR-Abs. 26 (50.0%) exhibited multi-domain recognition, with 1 patient specifically recognizing the CTLD8 domain. A significant association was observed between PLA2R1-Ab and CysR-Ab (r = 0.869, p < 0.001), as well as with anti-CTLD1 Ab (r = 0.803, p < 0.001). During a median follow-up of 11 months (IQR, 6.0-17.0), 27 patients (65.9%) experienced complete or partial nephrotic syndrome remission. Notably, the multi-domain recognition exhibited a reduced remission rate compared to the single-domain (44.44% vs. 82.61%, p = 0.011, alongside higher concentrations of anti-PLA2R1-Abs. A higher baseline level of anti-CTLD1 was notably linked to a lower likelihood of remission. In a univariate analysis, multi-domain recognition decreases the probability of remission (HR, 0.38 [95% CI, 0.16-0.87], p = 0.022). After the Kaplan-Meier analysis, the multi-domain group showed lower remission rates than the single-domain group at various time points.</p><p><strong>Conclusion: </strong>The PLA2R1 epitope spreading (ES) is a potent tool for monitoring disease severity and stratifying patients based on renal outcomes for prognostic purposes. Hence, we advocate evaluating ES at the baseline stage when determining early therapeutic interventions for individuals diagnosed with MN.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"543-554"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Renal Ischemia Induces Endoplasmic Reticulum Stress and Impairs the Reparative Potency of Scattered Tubular-Like Cells. 肾缺血诱导内质网应激,损害散在小管样细胞的修复能力。
IF 3.2 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2025-04-10 DOI: 10.1159/000545795
Alfonso Eirin, Sara Kazeminia, Barnit Kaur, Kumar Shivam, Xiang-Yang Zhu, Hui Tang, Kyra L Jordan, Shivam Bajpai, Ailing Xue, Alejandro R Chade, Maria V Irazabal, Lilach O Lerman, Alfonso Eirin
{"title":"Renal Ischemia Induces Endoplasmic Reticulum Stress and Impairs the Reparative Potency of Scattered Tubular-Like Cells.","authors":"Alfonso Eirin, Sara Kazeminia, Barnit Kaur, Kumar Shivam, Xiang-Yang Zhu, Hui Tang, Kyra L Jordan, Shivam Bajpai, Ailing Xue, Alejandro R Chade, Maria V Irazabal, Lilach O Lerman, Alfonso Eirin","doi":"10.1159/000545795","DOIUrl":"10.1159/000545795","url":null,"abstract":"<p><strong>Introduction: </strong>CD24+/CD133+ scattered tubular-like cells (STCs) are surviving renal cells that acquire progenitor-like characteristics to repair other damaged kidney cells. Renal artery stenosis (RAS) impairs the reparative capacity of STCs, but the underlying mechanisms remain unknown. STCs contain abundant endoplasmic reticulum (ER), but its capacity to fold proteins could become saturated (ER stress), leading to STC dysfunction. We hypothesized that RAS alters the expression of genes implicated in ER stress in swine STCs.</p><p><strong>Methods: </strong>STCs were harvested from pig kidneys after 10 weeks of RAS or sham (n = 6 each) and expression of ER stress genes was assessed using mRNA-seq (n = 3 each). To elucidate mechanisms regulating ER stress genes in RAS-STCs, integrated mRNA-seq/microRNA (miRNA)-seq and transcription factor (TF) prediction analysis were performed. STC ER stress was assessed in vitro using Western blotting, serial block-face electron microscopy, and mass spectrometry. The involvement of ER stress in regulating the STC-protective effects was also assessed in vitro by their capacity to improve viability of injured human tubular epithelial cells.</p><p><strong>Results: </strong>RAS pigs developed significant renal dysfunction. mRNA-seq identified 25 ER stress genes upregulated and 30 downregulated in RAS-STCs versus normal-STCs. miRNAs were found to target over a third of all differentially expressed ER stress genes, and almost half of genes encoding for the top 50 TFs involved in regulation of ER stress genes were dysregulated in RAS-STCs. RAS-STCs exhibited higher ER stress compared to normal-STCs, reflected in significant ER dilation and formation of ER-mitochondria contacts and increased levels of ER stress-related amino acids. Importantly, ER stress inhibition improved the reparative capacity of RAS-STCs in vitro.</p><p><strong>Conclusion: </strong>Renal ischemia alters expression of ER stress-related genes in swine STCs, likely through post-transcriptional- and TF-regulatory mechanisms, which induces ER stress and impairs their reparative potency. These alterations may limit the potential of STCs to repair damaged kidneys in subjects with RAS.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"657-673"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cross-Generational Impact of Maternal Exposure to Low Level of PM2.5 on Kidney Health. 母亲暴露于低浓度 PM2.5 对肾脏健康的跨代影响。
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2024-11-21 DOI: 10.1159/000542135
Hui Chen, Long The Nguyen, Min Feng, Baoming Wang, Bai Xu, Rochelle A Yarak, Yik Lung Chan, Seethalakshmi Viswanathan, Muralikrishna Gangadharan Komala, Carol A Pollock, Brian G Oliver, Sonia Saad
{"title":"Cross-Generational Impact of Maternal Exposure to Low Level of PM2.5 on Kidney Health.","authors":"Hui Chen, Long The Nguyen, Min Feng, Baoming Wang, Bai Xu, Rochelle A Yarak, Yik Lung Chan, Seethalakshmi Viswanathan, Muralikrishna Gangadharan Komala, Carol A Pollock, Brian G Oliver, Sonia Saad","doi":"10.1159/000542135","DOIUrl":"10.1159/000542135","url":null,"abstract":"<p><strong>Introduction: </strong>Inhaled fine and ultrafine particulate matter may affect organs other than the lung, including the kidney. Recent studies have consistently shown the possibility of air pollution in highly polluted countries to be nephrotoxic. However, in countries like Australia, where air quality generally adheres to or remains below the WHO standards, the subtle yet consequential impacts of chronic exposure to seemingly safe levels of traffic PM2.5, are a subject of increasing significance. However, how such exposures in the peri-pregnancy period affect kidney health in mothers and the offspring is unclear, which formed the aims of this study.</p><p><strong>Methods: </strong>Female Balb/c mice were exposed to PM2.5 (5 μg/day) delivered nasally for 6 weeks prior to mating, during gestation and lactation (PM group). In a subgroup, PM2.5 was switched to saline from mating until offspring were weaned to model mothers moving to areas with clean air. Kidneys were analysed in dams and adult offspring at 13 weeks of age.</p><p><strong>Results: </strong>PM2.5 induced oxidative stress without histological changes in the dam's kidney. However, male PM offspring displayed in utero underdevelopment, characterised by reduced body weight and kidney-to-body weight at birth compared to control offspring, and lower glomerular numbers, with a marked increase in albuminuria, glomerulosclerosis, inflammation, oxidative stress, and mitochondrial injury. Female PM offspring had delayed postnatal development, lower glomerular numbers, increased glomerulosclerosis, and oxidative stress injury markers. Removal of PM2.5 from conception significantly reduced DNA oxidation and kidney damage in the offspring.</p><p><strong>Conclusion: </strong>There is no safe level of ambient PM2.5 for kidney health when exposed in utero. Maternal PM2.5 exposure equally impacts the kidney health of male and female offspring. Removal of PM2.5 from conception was overall protective to the offspring.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"222-235"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Role of Neutrophils in Venous Thrombosis in Primary Membranous Nephropathy. 中性粒细胞在原发性膜性肾病静脉血栓形成中的作用。
IF 3.2 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2025-03-19 DOI: 10.1159/000545296
Xiaowei Yang, Qiuhan Wang, Benxia Bing, Liang Xu, Chenghua Wang, Chunjuan Zhai, Jing Sun, Xiaowei Yang
{"title":"The Role of Neutrophils in Venous Thrombosis in Primary Membranous Nephropathy.","authors":"Xiaowei Yang, Qiuhan Wang, Benxia Bing, Liang Xu, Chenghua Wang, Chunjuan Zhai, Jing Sun, Xiaowei Yang","doi":"10.1159/000545296","DOIUrl":"10.1159/000545296","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with primary membranous nephropathy (PMN) are at high risk of developing venous thromboembolic events (VTEs), while neutrophils are involved in the onset of VTEs in PMN remains unclear.</p><p><strong>Methods: </strong>The association of neutrophils with VTEs was retrospectively analyzed in a large cohort of patients with PMN. Plasma cell-free DNA (cfDNA) levels were evaluated in PMN patients with and without VTEs. In addition, we established a rat model of passive Heymann nephritis (PHN) by immunization with sheep anti-rat Fx1A serum. The inferior vena cava (IVC) was ligated to establish the deep vein thrombosis model. Thrombus weight and length were evaluated at 4 h after IVC stenosis in rats. GSK484 was administered via intraperitoneal injection to assess the role of NETosis inhibition in thrombosis formation in PHN rats.</p><p><strong>Results: </strong>Circulating neutrophils in PMN patients with VTEs were significantly higher than in patients without VTEs. Neutrophil counts were positively correlated with the activity of factor IX, factor XI, protein C, protein S, and AT-III (r = 0.328, p = 0.002; r = 0.378, p < 0.001; r = 0.380, p < 0.001; r = 0.243, p = 0.029; r = 0.254, p = 0.020). In multivariate logistic regression, neutrophils were the independent risk factors for VTEs in PMN patients (OR = 1.608, 95% CI: 1.293-2.000; p < 0.05). Significantly increased plasma levels of cfDNA were detected in PMN patients, especially in PMN patients with VTEs, relative to controls. In animal experiments, the plasma cfDNA levels elevated significantly after IVC stenosis in PHN rats, and GSK484 decreased the plasma cfDNA levels in PHN rats with IVC stenosis. Four hours after IVC stenosis surgery, thrombi formed in PHN rats were both longer and heavier compared to those observed in control rats, and GSK484 administration significantly inhibits the thrombus formation in PHN rats.</p><p><strong>Conclusion: </strong>This study preliminarily indicated that neutrophils were involved in the hypercoagulation state and increased thrombosis propensity in PMN, offering novel insights into the pathogenesis of thrombosis formation in PMN and potential therapeutic targets for its management.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"630-640"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DOT1L Regulates Cellular Senescence during the Progression from Acute Kidney Injury to Chronic Kidney Disease via the microRNA-222-5p/WNT9B Signaling Pathway. DOT1L通过micro-222-5p/WNT9B信号通路调控急性肾损伤向慢性肾病进展过程中的细胞衰老。
IF 3.2 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2025-02-12 DOI: 10.1159/000544694
Heng Jin, Congcong Yao, Wei Wei, Guoyu Wu, Yan Zhang, Keke Sun, Zhiyuan Liu, Yushanjiang Abudureheman, Heng Wu, Qi Lv, Ayinuer Paredong, Songtao Shou, Heng Jin
{"title":"DOT1L Regulates Cellular Senescence during the Progression from Acute Kidney Injury to Chronic Kidney Disease via the microRNA-222-5p/WNT9B Signaling Pathway.","authors":"Heng Jin, Congcong Yao, Wei Wei, Guoyu Wu, Yan Zhang, Keke Sun, Zhiyuan Liu, Yushanjiang Abudureheman, Heng Wu, Qi Lv, Ayinuer Paredong, Songtao Shou, Heng Jin","doi":"10.1159/000544694","DOIUrl":"10.1159/000544694","url":null,"abstract":"<p><strong>Introduction: </strong>Acute kidney injury (AKI) is a common clinical condition where cellular senescence plays a crucial role in its progression. Previous studies have suggested that DOT1L plays a pivotal role in cellular senescence, yet its specific mechanisms in regulating AKI cellular senescence remain unclear.</p><p><strong>Methods: </strong>This study utilized a glycerol-induced in vivo AKI model and employed the DOT1L-specific inhibitor EPZ004777 (EPZ) to suppress DOT1L function. Aging staining, periodic acid-Schiff staining, and Masson staining were employed to assess renal aging, injury, and interstitial fibrosis. In vitro experiments utilized doxorubicin-treated human renal tubular epithelial (HK-2) cells to establish an AKI cellular senescence model. EPZ was used to inhibit DOT1L, evaluating its impact on cellular senescence. High-throughput miRNA sequencing was performed to analyze differential expression of miRNAs downstream of DOT1L, and DOT1L overexpression and dual luciferase reporter gene experiments were conducted to explore interactions among DOT1L, miR-222-5p, and Wnt family member 9B (WNT9B).</p><p><strong>Results: </strong>The results demonstrated that in vivo inhibition of DOT1L significantly reduced cellular senescence and improved renal tubular injury and interstitial fibrosis. In the doxorubicin-induced HK-2 cell model, DOT1L inhibition markedly decreased cellular senescence and lowered mRNA and protein levels of senescence markers while alleviating cell cycle arrest. DOT1L inhibition notably upregulated miR-222-5p expression and suppressed WNT9B expression, with opposite effects observed with DOT1L overexpression.</p><p><strong>Conclusion: </strong>DOT1L regulates cellular senescence through the miR-222-5p/WNT9B pathway in AKI. These findings suggest that DOT1L may serve as a potential therapeutic target to mitigate the progression of AKI to chronic kidney disease.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"577-594"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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